Two major processes presumably located in the bile canalicular membrane initate and regulate hepatic bile flow. The present study is designed to examine the role of the putative bile acid receptor and the sodium pump, (Na-K)ATPase, in the regulation of bile flow. The importance of sodium gradients in the regulation of bile acid membrane translocation will be examined in hepatocytes, ileal and renal tubule cells. Bile acid receptors and (Na-K)ATPase will be quantitated under different pharmacological situations which are associated with altered bile flow. Transport of bile acids into cultured hepatocytes will be studied under defined conditions. Membrane vesicles will be prepared from hepatocytes, ileum and renal tubular cells to examine membrane transport in contra-lateral poles of the cell. The effect of phenobarbital, glucocorticoids, estrogens and thyroid hormone and high cholesterol diets on liver surface membrane structure and function will be examined.